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头孢曲松可减轻酒精戒断斑马鱼的焦虑样行为并增强大脑谷氨酸转运。

Ceftriaxone Attenuated Anxiety-Like Behavior and Enhanced Brain Glutamate Transport in Zebrafish Subjected to Alcohol Withdrawal.

机构信息

Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE, Brazil.

Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.

出版信息

Neurochem Res. 2020 Jul;45(7):1526-1535. doi: 10.1007/s11064-020-03008-z. Epub 2020 Mar 17.

DOI:10.1007/s11064-020-03008-z
PMID:32185643
Abstract

Chronic and/or excessive consumption of alcohol followed by reduced consumption or abstention can result in Alcohol Withdrawal Syndrome. A number of behavioral changes and neurological damage result from ethanol (EtOH) withdrawal. Ceftriaxone (Cef) modulates the activity of excitatory amino acid transporters by increasing their gene expression. Zebrafish are commonly used to study alcohol exposure. The aim of this study was to evaluate the influence of Cef (100 µM) on behavior patterns, glutamate transport activity, and oxidative stress in zebrafish brains subjected to EtOH (0.3% v/v) withdrawal. The exploratory tests using Novel tank showed that EtOH withdrawal promoted a decrease in the time spent and number of entries of in the bottom displaying an anxiety-like behavior. In contrast, treatment with Cef resulted in recovery of exploratory behavioral patterns. Ceftriaxone treatment resulted in increased glutamate uptake in zebrafish subjected to EtOH withdrawal. Furthermore, EtOH withdrawal increased reactive species, as determined using thiobarbituric acid and dichlorodihydrofluorescein assays. Treatment with Cef reversed these effects. Ceftriaxone promoted a significant reduction in brain sulfhydryl content in zebrafish subjected to EtOH withdrawal. Therefore, Cef treatment in conjunction with EtOH withdrawal induced anxiolytic-like effects due to possible neuromodulation of glutamatergic transporters, potentially through mitigation of oxidative stress.

摘要

慢性和/或过度饮酒,随后减少或戒酒后,可能会导致酒精戒断综合征。乙醇(EtOH)戒断会导致许多行为改变和神经损伤。头孢曲松(Cef)通过增加其基因表达来调节兴奋性氨基酸转运体的活性。斑马鱼常用于研究酒精暴露。本研究旨在评估头孢曲松(100μM)对接受 0.3%(v/v)乙醇戒断的斑马鱼大脑行为模式、谷氨酸转运活性和氧化应激的影响。使用新鱼缸进行的探索性测试表明,乙醇戒断导致在鱼缸底部停留时间和进入次数减少,表现出焦虑样行为。相比之下,Cef 处理导致探索性行为模式的恢复。头孢曲松处理导致接受乙醇戒断的斑马鱼的谷氨酸摄取增加。此外,使用硫代巴比妥酸和二氯荧光素测定法测定,乙醇戒断增加了活性物质。Cef 处理逆转了这些影响。头孢曲松在接受乙醇戒断的斑马鱼中促进了大脑巯基含量的显著减少。因此,Cef 治疗与乙醇戒断联合诱导了类似焦虑的作用,可能是通过减轻氧化应激来调节谷氨酸转运体的神经调节。

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